Loading…
Identification and validation of novel serum markers for early diagnosis of endometriosis
BACKGROUND Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential...
Saved in:
Published in: | Human reproduction (Oxford) 2012-02, Vol.27 (2), p.408-417 |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43 |
---|---|
cites | cdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43 |
container_end_page | 417 |
container_issue | 2 |
container_start_page | 408 |
container_title | Human reproduction (Oxford) |
container_volume | 27 |
creator | Gajbhiye, R. Sonawani, A. Khan, S. Suryawanshi, A. Kadam, S. Warty, N. Raut, V. Khole, V. |
description | BACKGROUND
Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis.
METHODS
A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation.
RESULTS
The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis.
CONCLUSIONS
Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis. |
doi_str_mv | 10.1093/humrep/der410 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_916530070</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/humrep/der410</oup_id><sourcerecordid>916530070</sourcerecordid><originalsourceid>FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</originalsourceid><addsrcrecordid>eNqF0D1PwzAQBmALgWgpjKwoC4Il9OzYTjKiio9KlVhgYIpc-wKGJC52Uqn_nkQpMDLZPj0--15CzincUMiT-XtXe9zMDXpO4YBMKZcQs0TAIZkCk1lMqaQTchLCB0C_zeQxmTBGRQaZmJLXpcGmtaXVqrWuiVRjoq2qrBmProwat8UqCui7OqqV_0QfotL5CJWvdpGx6q1xwYaBYmNcja23Q-GUHJWqCni2X2fk5f7uefEYr54elovbVaw5gzZOjaR5oikFRk2aJ5LlKUjDjZQa14IbZEJQgJQxpTUTPEk5k2WZ6ZxDtubJjFyNfTfefXUY2qK2QWNVqQZdF4qcSpH096GX8Si1dyF4LIuNt_1Iu4JCMYRZjGEWY5i9v9h37tY1ml_9k14PLvdABa2q0qtG2_DnxPBblvfuenSu2_zz5jdipYyi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>916530070</pqid></control><display><type>article</type><title>Identification and validation of novel serum markers for early diagnosis of endometriosis</title><source>Oxford Journals Online</source><creator>Gajbhiye, R. ; Sonawani, A. ; Khan, S. ; Suryawanshi, A. ; Kadam, S. ; Warty, N. ; Raut, V. ; Khole, V.</creator><creatorcontrib>Gajbhiye, R. ; Sonawani, A. ; Khan, S. ; Suryawanshi, A. ; Kadam, S. ; Warty, N. ; Raut, V. ; Khole, V.</creatorcontrib><description>BACKGROUND
Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis.
METHODS
A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation.
RESULTS
The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis.
CONCLUSIONS
Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.</description><identifier>ISSN: 0268-1161</identifier><identifier>EISSN: 1460-2350</identifier><identifier>DOI: 10.1093/humrep/der410</identifier><identifier>PMID: 22158085</identifier><identifier>CODEN: HUREEE</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Antibody Specificity ; Autoantibodies - analysis ; Autoantigens - blood ; Autoantigens - chemistry ; Biological and medical sciences ; Biomarkers - blood ; Biomarkers - chemistry ; Blood Proteins - chemistry ; Cohort Studies ; Cross-Sectional Studies ; Early Diagnosis ; Endometriosis - blood ; Endometriosis - diagnosis ; Endometriosis - physiopathology ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Immunodominant Epitopes - analysis ; Immunodominant Epitopes - chemistry ; Medical sciences ; Membrane Proteins - blood ; Membrane Proteins - chemistry ; Peptide Fragments - analysis ; Peptide Fragments - chemistry ; Peptide Mapping ; Sensitivity and Specificity ; Severity of Illness Index ; Tropomodulin - blood ; Tropomodulin - chemistry ; Tropomyosin - blood ; Tropomyosin - chemistry ; Young Adult</subject><ispartof>Human reproduction (Oxford), 2012-02, Vol.27 (2), p.408-417</ispartof><rights>The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</citedby><cites>FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25543729$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22158085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gajbhiye, R.</creatorcontrib><creatorcontrib>Sonawani, A.</creatorcontrib><creatorcontrib>Khan, S.</creatorcontrib><creatorcontrib>Suryawanshi, A.</creatorcontrib><creatorcontrib>Kadam, S.</creatorcontrib><creatorcontrib>Warty, N.</creatorcontrib><creatorcontrib>Raut, V.</creatorcontrib><creatorcontrib>Khole, V.</creatorcontrib><title>Identification and validation of novel serum markers for early diagnosis of endometriosis</title><title>Human reproduction (Oxford)</title><addtitle>Hum Reprod</addtitle><description>BACKGROUND
Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis.
METHODS
A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation.
RESULTS
The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis.
CONCLUSIONS
Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.</description><subject>Adult</subject><subject>Antibody Specificity</subject><subject>Autoantibodies - analysis</subject><subject>Autoantigens - blood</subject><subject>Autoantigens - chemistry</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - chemistry</subject><subject>Blood Proteins - chemistry</subject><subject>Cohort Studies</subject><subject>Cross-Sectional Studies</subject><subject>Early Diagnosis</subject><subject>Endometriosis - blood</subject><subject>Endometriosis - diagnosis</subject><subject>Endometriosis - physiopathology</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunodominant Epitopes - analysis</subject><subject>Immunodominant Epitopes - chemistry</subject><subject>Medical sciences</subject><subject>Membrane Proteins - blood</subject><subject>Membrane Proteins - chemistry</subject><subject>Peptide Fragments - analysis</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Mapping</subject><subject>Sensitivity and Specificity</subject><subject>Severity of Illness Index</subject><subject>Tropomodulin - blood</subject><subject>Tropomodulin - chemistry</subject><subject>Tropomyosin - blood</subject><subject>Tropomyosin - chemistry</subject><subject>Young Adult</subject><issn>0268-1161</issn><issn>1460-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqF0D1PwzAQBmALgWgpjKwoC4Il9OzYTjKiio9KlVhgYIpc-wKGJC52Uqn_nkQpMDLZPj0--15CzincUMiT-XtXe9zMDXpO4YBMKZcQs0TAIZkCk1lMqaQTchLCB0C_zeQxmTBGRQaZmJLXpcGmtaXVqrWuiVRjoq2qrBmProwat8UqCui7OqqV_0QfotL5CJWvdpGx6q1xwYaBYmNcja23Q-GUHJWqCni2X2fk5f7uefEYr54elovbVaw5gzZOjaR5oikFRk2aJ5LlKUjDjZQa14IbZEJQgJQxpTUTPEk5k2WZ6ZxDtubJjFyNfTfefXUY2qK2QWNVqQZdF4qcSpH096GX8Si1dyF4LIuNt_1Iu4JCMYRZjGEWY5i9v9h37tY1ml_9k14PLvdABa2q0qtG2_DnxPBblvfuenSu2_zz5jdipYyi</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Gajbhiye, R.</creator><creator>Sonawani, A.</creator><creator>Khan, S.</creator><creator>Suryawanshi, A.</creator><creator>Kadam, S.</creator><creator>Warty, N.</creator><creator>Raut, V.</creator><creator>Khole, V.</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Identification and validation of novel serum markers for early diagnosis of endometriosis</title><author>Gajbhiye, R. ; Sonawani, A. ; Khan, S. ; Suryawanshi, A. ; Kadam, S. ; Warty, N. ; Raut, V. ; Khole, V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Antibody Specificity</topic><topic>Autoantibodies - analysis</topic><topic>Autoantigens - blood</topic><topic>Autoantigens - chemistry</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - chemistry</topic><topic>Blood Proteins - chemistry</topic><topic>Cohort Studies</topic><topic>Cross-Sectional Studies</topic><topic>Early Diagnosis</topic><topic>Endometriosis - blood</topic><topic>Endometriosis - diagnosis</topic><topic>Endometriosis - physiopathology</topic><topic>Female</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunodominant Epitopes - analysis</topic><topic>Immunodominant Epitopes - chemistry</topic><topic>Medical sciences</topic><topic>Membrane Proteins - blood</topic><topic>Membrane Proteins - chemistry</topic><topic>Peptide Fragments - analysis</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Mapping</topic><topic>Sensitivity and Specificity</topic><topic>Severity of Illness Index</topic><topic>Tropomodulin - blood</topic><topic>Tropomodulin - chemistry</topic><topic>Tropomyosin - blood</topic><topic>Tropomyosin - chemistry</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gajbhiye, R.</creatorcontrib><creatorcontrib>Sonawani, A.</creatorcontrib><creatorcontrib>Khan, S.</creatorcontrib><creatorcontrib>Suryawanshi, A.</creatorcontrib><creatorcontrib>Kadam, S.</creatorcontrib><creatorcontrib>Warty, N.</creatorcontrib><creatorcontrib>Raut, V.</creatorcontrib><creatorcontrib>Khole, V.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human reproduction (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gajbhiye, R.</au><au>Sonawani, A.</au><au>Khan, S.</au><au>Suryawanshi, A.</au><au>Kadam, S.</au><au>Warty, N.</au><au>Raut, V.</au><au>Khole, V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and validation of novel serum markers for early diagnosis of endometriosis</atitle><jtitle>Human reproduction (Oxford)</jtitle><addtitle>Hum Reprod</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>27</volume><issue>2</issue><spage>408</spage><epage>417</epage><pages>408-417</pages><issn>0268-1161</issn><eissn>1460-2350</eissn><coden>HUREEE</coden><abstract>BACKGROUND
Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis.
METHODS
A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation.
RESULTS
The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis.
CONCLUSIONS
Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22158085</pmid><doi>10.1093/humrep/der410</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0268-1161 |
ispartof | Human reproduction (Oxford), 2012-02, Vol.27 (2), p.408-417 |
issn | 0268-1161 1460-2350 |
language | eng |
recordid | cdi_proquest_miscellaneous_916530070 |
source | Oxford Journals Online |
subjects | Adult Antibody Specificity Autoantibodies - analysis Autoantigens - blood Autoantigens - chemistry Biological and medical sciences Biomarkers - blood Biomarkers - chemistry Blood Proteins - chemistry Cohort Studies Cross-Sectional Studies Early Diagnosis Endometriosis - blood Endometriosis - diagnosis Endometriosis - physiopathology Female Gynecology. Andrology. Obstetrics Humans Immunodominant Epitopes - analysis Immunodominant Epitopes - chemistry Medical sciences Membrane Proteins - blood Membrane Proteins - chemistry Peptide Fragments - analysis Peptide Fragments - chemistry Peptide Mapping Sensitivity and Specificity Severity of Illness Index Tropomodulin - blood Tropomodulin - chemistry Tropomyosin - blood Tropomyosin - chemistry Young Adult |
title | Identification and validation of novel serum markers for early diagnosis of endometriosis |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T03%3A37%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identification%20and%20validation%20of%20novel%20serum%20markers%20for%20early%20diagnosis%20of%20endometriosis&rft.jtitle=Human%20reproduction%20(Oxford)&rft.au=Gajbhiye,%20R.&rft.date=2012-02-01&rft.volume=27&rft.issue=2&rft.spage=408&rft.epage=417&rft.pages=408-417&rft.issn=0268-1161&rft.eissn=1460-2350&rft.coden=HUREEE&rft_id=info:doi/10.1093/humrep/der410&rft_dat=%3Cproquest_cross%3E916530070%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c420t-7d6193c11021d793629706d4d66ceb54de255100722acc25437426ff8c9408b43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=916530070&rft_id=info:pmid/22158085&rft_oup_id=10.1093/humrep/der410&rfr_iscdi=true |